The Lirin culture has a delicately balanced finite population where everyone serves a specific function. After making contact with the Federation in 2225, the Lirin generated Nano to serve as their emissary to the Federation. This meant Nano could never return home, as he would disrupt the balance. (EVcomics: "Flesh of My Flesh", "One of a Kind")

Nano joined the crew of the Enterprise in 2251, when it re-launched on a five-year mission after Captain Pike assumed command.

On the Enterprise's next mission Nano was again a member of a landing party, this time to investigate a loss of communications with Project Pharos. After boarding the Pharos lighthouse the party came under attack by Klingon team who had attacked the facility. When EnsignRaeger was shot by Klingons as they announced their presence, Nano exclaimed "By the Unity!" (EVcomic: "The Fires of Pharos")

Shortly afterward, he was among the crew taking shore leave on Rigel VII on the eve of the planet's admission into the Federation. Unfortunately rogue elements of the Rigellian warrior caste, the Kaylar, were not content to let their traditions die out and began a coup. Crew persons from the Enterprise were attacked and Nano received a head wound' damaging his chitin' while he was distracted using his pyrotechnic abilities to save Spock from a Kaylar attack. Nevertheless Nano was still sufficiently functional to modify a communicator so that YeomanDermot Cusack could track down a Rigellian jamming device and call in aid from the Enterprise. (EVcomic: "Our Dearest Blood")

Later that year Nano was summoned back to his homeworld, after the unexpected death of a member of the Lirin Unity. Nano was to act as replacement, but the shared consciousness of the worldmind repelled his attempts to rejoin it. With the help of Spock and José Tyler, he learned that the deaths were outbursts of the Unity's uncontrollable fear of the outside world. He suggested the insular Unity ask the Federation for help, and he rejoined the Enterprise crew. (EVcomic: "One of a Kind")